Mutation found

Polymyositis research (Dr. Peter Leegwater, Drs. Yvet Opmeer & Dr. Paul Mandigers)

There is some good news. We have found the mutation that can be associated with polymyositis. All the dogs with polymyositis which are examined by use have the mutation. This mutation is can be found close to two important genes involved in the functioning of the immune system. It also turns out that Kooikerhondjes suffering from polymyositis have an abnormal function of these two genes. So the mutation has no doubt a meaning. However, not all the Kooikerhondjes with this mutation become ill. Kooikerhondjes that are homozygous for this mutation (they therefore have the two different alleles) have an increased risk, but not all of them will get sick. We see this more often with immune-mediated diseases.

Environmental factors or variations in the rest of the DNA can cause a dog to become ill or not. That is why we call this mutation a risk factor. Also heterozygous Kooikerhondjes (Kooikerhondjes with only one deviating allele) are also at risk. That risk is very small (probably less than 1 percent) but present. Because there are many Kooikerhondjes with this mutation, we see that about 1 in 3 leaders of polymyositis is heterozygous (carrier) for the hereditary risk factor.

Pedigree research showed that other factors must play a role. We noticed for example that in some litters several dogs got sick, which would not make sense if the mutation is only expressed in a small proportion of the Kooikerhondjes. However, if there is a variation in the DNA that makes a dog more at risk or less at risk, this explains what we see in some litters.

In order to investigate this factor the DNA of a group of heterozygous leaders was compared to a group of homozygous leaders which have remained healthy throughout their lives. This comparison led to signals on two chromosomes that have been further investigated. The first signal led to a DNA variant that seemed promising, but it turned out that it had a high frequency in the entire population. It was a false positive result that was a coincidental. The second signal could not yet be traced back to a variant in a gene. This investigation will be continued.

Improvement in the treatment of Kooikerhondjes with polymyositis (Dr. Paul Mandigers)

In recent years we have seen several Kooikerhondjes with polymyositis. In the early years of this study, the treatment results were downright appalling. Not infrequently, a dog did not or hardly responded to the chosen prednisolone therapy. You expect this with an immune-mediated disease such as polymyositis. The treatment results did improve when we also treated with certain muscle supplements. And based on the pathology result, we could also reasonably predict whether or not a dog would respond.

Thanks to the research by Dr. Leegwater and Drs. Yvet Opmeer (then a student), the hereditary risk factor was identified. Because the two genes immediately adjacent to this mutation functioned abnormally, we started treating Kooikerhondjes with a specific inhibitor of these genes. And so far, the results seem very hopeful.

Meanwhile, we have treated various Kooikerhondjes in various countries and some dogs recover in such a way that the owners report that they no longer notice something about their dog. A hopeful result! Of course the goal remains to combat the mutation, but given the wide distribution of the mutation this requires several generations.